The overall objective of this project is to better define translational control of protein synthesis, particularly as it applies to the understanding of the pathogenesis of illnesses manifested by decreased heme synthesis. Specifically, this proposal is concerned with the role of the mitochondrial inner membrane in regulating cellular heme concentration and heme control of translation of protein synthesis via the hemin controlled repressor. Three basic systems will initially be used: 1) mitochondria isolated from rat liver; 2) dispersed in vitro rat liver hepatic cells; 3) in vivo labeling of cytoplasmic and mitochondrial synthetic products. Studies will be directed towards understanding the decreased ability in iron deficiency to synthesize the proteins of the inner mitochondrial membrane and how this relates to cytoplasmic heme and protein synthesis. Specifically, the mitochondrial heme synthetic enzymes as well as polyacrylamide gel electrophoresis of the mitochondrial membrane proteins will be investigated and correlated to a decrease in mitochondrial protein synthesis and appearance of the hemin controlled repressor. After these studies are completed, attention will be directed towards the effects of various heme synthesis inhibitors (e.g. alcohol, benzene) and stimulators (e.g. cyclic AMP) on mitochondrial protein synthesis and the relationship thereby to cytoplasmic heme control of protein synthesis. Finally, attention will be directed towards investigating the mechanism whereby the inner mitochondrial membrane of erythroid precursors likewise controls heme synthesis and, thus, cytoplasmic protein synthesis.